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Ipsilateral activation of the unaffected motor cortex in patients with hemiparetic stroke.

BACKGROUND AND PURPOSE: Recent research has shown that following stroke patients can display ipsilateral activity reflecting a functional link between the undamaged hemisphere and the affected upper limb on the same side of the body. In the present study the capacity for ipsilateral activation is documented during recovery by using transcranial magnetic stimulation (TMS) and transcranial Doppler (TCD). METHODS: Fourteen patients affected by hemispheric stroke were examined with TMS and TCD within 48 h of onset, and again 6 months later. Neurological signs were scored with reference to the NIHSS, and patients executed a thumb to finger opposition task so as to further estimate the motor deficit. Twenty healthy volunteers represented the control population. RESULTS: (1) Both TMS and TCD yielded homogeneous results showing ipsilateral activity between affected hands and undamaged hemispheres. On stimulating the motor cortex 3 cm anterior and 3 cm lateral to Cz, a scalp site remote from the primary motor area, ipsilateral motor evoked potentials (iMEPs) from hand muscles were found in recovered patients. (2) In 8 controls iMEPs with smaller amplitudes than patients could be obtained by stimulating only the left hemisphere. (3) TCD revealed increased blood flow velocity in the ipsilateral MCA by activating the recovering hand (10.5+/-3.3%; P<0.001). CONCLUSION: TMS reveals a specific area in the motor cortex from which ipsilateral MEPs can be elicited and both TMS and TCD indicate that an ipsilateral corticospinal tract can be accessible in some adult controls or becomes unmasked after cerebral damage.

Aged↗

Red nucleus lesions do not affect limb preference or use, but exacerbate the effects of motor cortex lesions on grasping in the rat.

The corticospinal and rubrospinal systems are thought to collaborate in the production of skilled forelimb movements in primates. This study examined whether this relation holds in rodents. Limb preference and limb skill were assessed in a reaching-for-food task in rats with ibotenic acid lesions of the red nucleus or combined red nucleus lesions and aspirative motor cortex lesions. Major findings were: (1) Unilateral red nucleus lesions did not influence subsequent development of limb preference in naive rats. (2) Unilateral red nucleus lesions in pretrained rats failed to affect the incidence of reaching (total reaches) and reaching success (hit percent) by either the contralateral or ipsilateral limb. (3) Whereas motor cortex lesions impaired subsequent use of the contralateral limb, additional red nucleus lesions did not change total reaches or hit percent, but did produce moderate qualitative changes in limb accuracy and paw opening during grasping. The results demonstrate that in the rat, the red nucleus is not essential for the ballistic component of reaching but may contribute to fine motor control.

Animals↗

Neural activity in human primary motor cortex areas 4a and 4p is modulated differentially by attention to action.

The mechanisms underlying attention to action are poorly understood. Although distracted by something else, we often maintain the accuracy of a movement, which suggests that differential neural mechanisms for the control of attended and nonattended action exist. Using functional magnetic resonance imaging (fMRI) in normal volunteers and probabilistic cytoarchitectonic maps, we observed that neural activity in subarea 4p (posterior) within the primary motor cortex was modulated by attention to action, while neural activity in subarea 4a (anterior) was not. The data provide the direct evidence for differential neural mechanisms during attended and unattended action in human primary motor cortex.

Adult↗

Disinhibition of the contralateral motor cortex by low-frequency rTMS.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) results in a lasting decrease of motor evoked potentials (MEPs). Here we investigated the effects of supra-threshold rTMS (15 min, 1 Hz) to the left M1 on the excitability of the stimulated and homologous (unstimulated) M1 in healthy subjects by using single and double pulse TMS before and after rTMS. We found reduction of MEP amplitudes on the stimulated side and, most importantly, disinhibition of intracortical excitability of the homologous M1. This crossed effect of rTMS supports the concept of a physiological balance of reciprocal inhibitory projections and emphasizes that rTMS can induce remote effects that are relevant for the physiological interpretation of such interventions.

Adult↗

Motor neuron diseases: comparison of single-voxel proton MR spectroscopy of the motor cortex with MR imaging of the brain.

PURPOSE: To evaluate single-voxel proton magnetic resonance (MR) spectroscopy in detection of abnormality of the upper motor neuron in patients with motor neuron diseases. MATERIALS AND METHODS: In 43 of 50 patients with motor neuron disease and 14 of 14 control subjects, matching sets of MR spectra were obtained in the left and right motor cortex. The ratio of N-acetylaspartate (NAA) to creatine (Cr) was derived from peak area measurements. Mean ratios were calculated for control subjects and several patient groups, including patients with amyotrophic lateral sclerosis (ALS) or primary lateral sclerosis (PLS). MR images were evaluated for corticospinal tract hyperintensity and central sulcus dilatation. RESULTS: Mean NAA/Cr values were significantly different between control subjects and the ALS or PLS groups (P < .05). With an optimal cutoff of 2.5, NAA/Cr values were abnormal in 15 (79%) of 19 patients with ALS, 12 (67%) of 18 patients with PLS, and one (7%) of 14 control subjects. Corticospinal tract hyperintensity, central sulcus enlargement, or both were found in 43% of the ALS group, 24% of the PLS group, and 7% of the control group. CONCLUSION: NAA/Cr values determined at single-voxel proton MR spectroscopy are more sensitive than are standard findings at MR imaging in the detection of upper motor neuron disease.

Aged↗

[Application of transcranial magnetic stimulation for monitoring of the motor cortex condition in dynamics in healthy subjects].

Transcranial magnetic stimulation (TMS) is used already for sixteen years for studying human central nervous system. The main objective of this work was to study motor thresholds and their hemispheric asymmetry in healthy subjects during TMS. We examined 31 righthanded healthy students. Their motor thresholds were measured in May (before vacations), September (immediately after vacations), and November (two months after vacations). Magnetic stimulator Neurosoft-MS (Ivanovo, Russia) was used for TNS of the motor cortex. It was shown that in the absence of regular active functional loads on the right hand, the motor thresholds in healthy righthanders significantly increased under the TMS of the left hemisphere, and hemispheric asymmetry disappeared under conditions both of muscle relaxation and voluntary contraction. Motor thresholds under the left-side TMS decreased and hemispheric asymmetry recovered with the restart of the regular active functional loads on the right hand.

Adult↗

Modulation of postural wrist tremors by magnetic stimulation of the motor cortex in patients with Parkinson's disease or essential tremor and in normal subjects mimicking tremor.

The effect of magnetic brain stimulation on postural wrist tremor was studied in 10 patients with Parkinson's disease, 12 with hereditary essential tremor, and 10 normal subjects who mimicked tremor by making rapid alternating wrist movements. In all patients and normal subjects, magnetic brain stimulation over the contralateral motor cortex at an intensity approximately 10% above threshold produced the following sequence of events: (1) a small direct electromyographic (EMG) response, followed by (2) suppression of the rhythmic EMG activity responsible for the tremor, before (3) reappearance of the tremor time-locked to the stimulus. It is concluded that magnetic brain stimulation over the motor cortex can modulate the oscillatory mechanisms responsible for the generation of postural tremors. Group analysis revealed that the time to reappearance of rhythmic EMG activity varied significantly with the period of parkinsonian postural tremors, but not with the period of essential or mimicked tremors. Magnetic stimulation also significantly shortened the period of parkinsonian postural tremors, but did not influence the period of essential or mimicked tremors. These behavioral differences indicate differences in the pathophysiological mechanisms underlying parkinsonian postural tremor and essential tremor.

Adult↗

Magnetic stimulation of motor cortex and nerve roots in children. Maturation of cortico-motoneuronal projections.

Magnetoelectrical stimulation of motor cortex and peripheral nerve roots was used to establish the maturational profiles of central and peripheral nervous system conduction times in normal children in upper and lower extremity muscles. To obtain true central conduction times, not contaminated by variation due to different preinnervational levels, a protocol using stimulation under full muscular relaxation was used. With this protocol clear responses of the upper extremity could be obtained after the first year of life, whereas in the lower extremity they could not be obtained before the fourth year of life. The developmental profile of central conduction times to upper and lower extremity muscles showed an age-dependent acceleration with adult values not being reached before the age of about 10 years. In contrast, peripheral conduction times obtained after cervical or lumbar root stimulation to upper and lower extremities showed a much faster maturational profile, with adult values being reached at about the age of 3 years. The data are discussed in relation to the available literature on neuromorphological development and provide normative values for the understanding of normal development of motor control in children as well as for application of this technique in children with motor disturbances.

Adolescent↗

Immunohistological evidences of Ginkgo biloba extract altering Bax to Bcl-2 expression ratio in the hippocampus and motor cortex of senescence accelerated mice.

Ginkgo biloba extract 761 appears to display neuroprotective effect in many nervous diseases and aging. Deterioration of mental functions during aging is always accompanied by loss of neurons, presumably through apoptosis. Here, we studied the effect of G. biloba extract in the expression of Bax/Bcl-2 ratio, an important apoptotic index, in the hippocampus and motor cortex of the aging brain. Bax and Bcl-2 expressions were examined with immunohistochemical methods. Senescence Accelerated Mice Prone Strain 8 was used because the aging process was accelerated with neuropathological alterations similar to those found in the aging human brain. The mice were fed with either G. biloba extract or sucrose from the age of 3 weeks until sacrifice at 3 or 9 months old. In the hippocampus of G. biloba fed 9-month-old mice, the ratio of Bax positive cell to Bcl-2 positive cell (Bax/Bcl-2 expression ratio) was 11.43 +/- 3.11 (mean +/- SD); significantly lower (P < 0.05) than the Bax/Bcl-2 expression ratio of 20.99 +/- 5.34 in the sucrose fed mice. The Bax/Bcl-2 expression cell ratios, however, in the motor cortex were not significantly different between the two groups (2.22 +/- 1.35 versus 2.27 +/- 2.02 for the G. biloba and the sucrose fed mice, respectively). The decrease in the Bax/Bcl-2 expression cell ratio following G. biloba treatment might hence be able to protect the aging hippocampus from moving further down the apoptotic pathway. Western blotting confirmed the decrease of Bax in the brain even after a short term and high dose Ginkgo treatment. It is speculated that the G. biloba extract may be a potential neuroprotective agent against apoptosis through the differential expressions of the Bax and Bcl-2 in the hippocampus.

Animals↗

Changes in the temporal pattern of primary motor cortex activity in a directional isometric force versus limb movement task.

We recorded the activity of 75 proximal-arm-related cells in caudal primary motor cortex (MI) while a monkey generated either isometric forces or limb movements against an inertial load. The forces and movements were in eight directions in a horizontal plane. The isometric force generated at the hand increased monotonically in the direction of the target force level. The force exerted against the load in the movement task was more complex, including a transient decelerative phase during the movement as the hand approached the target. Electromyographic (EMG) activity of proximal-arm muscles reflected the task-dependent changes in dynamics, showing a ramp increase in activity during the isometric task and a reciprocal triphasic burst pattern in the movement task. A sliding 50-ms window analysis showed that the directionality of the EMG, when expressed in hand-centered spatial coordinates, remained stable throughout the isometric ramp but often showed a significant transient shift during the limb movements. Many cells in M1 showed corresponding significant changes in activity pattern and instantaneous directionality between the two tasks. This momentary dissociation of discharge from the directional kinematics of hand displacement is evidence that the activity of many single proximal-arm related M1 cells is not coupled only to the direction and velocity of hand motion.

Animals↗

Analogous corticocortical inhibition and facilitation in ipsilateral and contralateral human motor cortex representations of the tongue.

How the human brain controls activation of the ipsilateral part of midline muscles is unknown. We studied corticospinal and corticocortical network excitability of both ipsilateral and contralateral motor representations of the tongue to determine whether they are under analogous or disparate inhibitory and facilitatory corticocortical control. Motor evoked potentials (MEPs) to unilateral focal transcranial magnetic stimulation (TMS) of the tongue primary motor cortex were recorded simultaneously from the ipsilateral and contralateral lingual muscles. Single-pulse TMS was used to assess motor threshold (MT) and MEP recruitment. Paired-pulse TMS was used to study intracortical inhibition (ICI) and intracortical facilitation (ICF) at various interstimulus intervals (ISIs) between the conditioning stimulus (CS) and the test stimulus (TS), and at different CS and TS intensities, respectively. Focal TMS invariably produced MEPs in both ipsilateral and contralateral lingual muscles. MT was lower and MEP recruitment was steeper when recorded from the contralateral muscle group. ICI and ICF were identical in the ipsilateral and contralateral representations, with inhibition occurring at short ISIs (2 and 3 ms) and facilitation occurring at longer ISIs (10 and 15 ms). Moreover, changing one stimulus parameter regularly produced analogous changes in MEP size bilaterally, revealing strong linear correlations between ipsilateral and contralateral ICI and ICF (P < 0.0001). These findings indicate that the ipsilateral and contralateral representations of the tongue are under analogous inhibitory and facilitatory control, possibly by a common intracortical network.

Adult↗

Cutaneous inputs can activate the ipsilateral primary motor cortex during bimanual sensory-driven movements in humans.

Using transcranial magnetic stimulation (TMS), we examined whether sensory input from a finger affects activity of the ipsilateral primary motor cortex (M1) when human subjects hold a virtual object bimanually and whether this ipsilateral activation varies under different contexts. Subjects used both index fingers to hold two plates, which were subjected to unpredictable pulling loads from torque motors. Loads were delivered in a random sequence to either plate or concurrently to both, although the latter occurred most frequently. Finger forces vertical to the plates and surface electromyographs from the first dorsal interosseous muscles were recorded bilaterally during the task. TMS was sometimes applied over the finger area of the left M1 at variable times relative to load onset to examine cortical excitability. Strength of TMS was set around the active motor threshold of the right finger muscle while subjects waited for loading to the handheld plates. When one plate was singly loaded, the M1 contralateral to the loaded finger was activated, causing automatic force increases in the finger. In addition, the ipsilateral M1 was activated during such loading, associated with transient force increases in the contralateral nonloaded finger. Activations in the ipsilateral M1 were also observed during concurrent loading, when activations were stronger than those following single loading of the contralateral plate. Ipsilateral activations weakened when concurrent loading was less frequent. These results suggest interactions between bilateral sensorimotor cortices during bimanual coordinated movements, with strength varying by context.

Adult↗

Unilateral upper limb asterixis related to primary motor cortex infarction.

BACKGROUND: Unilateral upper limb asterixis related to cortical infarct is an unusual clinical picture. We found this association in two patients. Magnetic resonance imaging (MRI), somatosensory evoked potentials (SEPs), and electromyographic recording were performed. CASE DESCRIPTIONS: Two patients developed an acute upper limb ataxia with asterixis. This consisted of frequent arrhythmic loss of extensor muscle tone on instruction to maintain the wrist and fingers extended. Voluntary electromyographic activity in the left extensor digitorum communis muscle showed abrupt periods of interruption ranging from 90 to 260 milliseconds in duration in the first case and from 60 to 220 milliseconds in the second case. SEPs were normal. MRI disclosed a right cortical infarct within the primary motor cortex in both cases. CONCLUSIONS: These findings indicate that asterixis was not related to a failure in the processing of proprioceptive input controlling the regulation of postural tone of the distal upper limbs because SEPs were normal. The involvement of primary motor cortex might suggest that asterixis results from an impairment of a centrally generated motor-command signal controlling the postural tone of the distal upper limb.

Aged↗

Interhemispheric inhibition in distal and proximal arm representations in the primary motor cortex.

Interhemispheric inhibitory interactions (IHI) operate between homologous distal hand representations in primary motor cortex (M1). It is not known whether proximal arm representations exhibit comparable effects on their homologous counterparts. We studied IHI in different arm representations, targeting triceps brachii (TB, n = 13), first dorsal interosseous (FDI, n = 13), and biceps brachii (BB, n = 7) muscles in healthy volunteers. Transcranial magnetic stimulation test stimuli (TS) were delivered to M1 contralateral to the target muscle preceded 10 ms by a conditioning stimulus (CS) to the opposite M1 at 110-150% resting motor threshold (RMT). IHI was calculated as the ratio between motor-evoked potential (MEP) amplitudes in conditioned relative to unconditioned trials. Mean RMTs were 38.9, 46.9, and 46.0% of stimulator output in FDI, TB, and BB muscles, respectively. IHI was 0.45 +/- 0.41 (FDI), 0.78 +/- 0.38 (TB), and 0.52 +/- 0.32 (BB, P < 0.01) when test MEP amplitudes were matched and 0.28 +/- 0.17 (FDI) and 0.85 +/- 0.31 (TB, P < 0.05) when TS intensities expressed as percentage RMT were matched. Significant IHI (P < 0.05) was identified with minimal CS intensities (expressed as percentage stimulator output) in the 30 s for FDI, 60 s for TB, and 40 s for BB. Additionally, a CS of roughly 120% RMT suppressed the test MEP but not a test H-reflex in BB, suggesting IHI observed in BB is likely mediated by a supraspinal mechanism. We conclude that IHI differs between different arm muscle representations, comparable between BB and FDI but lesser for TB. This finding suggests the amount of IHI between different arm representations does not strictly follow a proximal-to-distal gradient, but may be related to the role of each muscle in functional movement synergies.

Adult↗

Protective sensitivity changes of the motor cortex due to epileptiform experience of the visual cortex.

In awake rats, experiments were performed to study early epileptiform events (interictal spike, myoclonic jerk) in relation to a) the strength of the convulsive stimulus, b) the site of the focus, and c) epileptiform experience. For this reason, Na-penicillin G (PCN) was injected either into the motor or visual cortex and, in a second test 2 weeks thereafter, into the motor cortex in all these rats. The median latencies of both the first interictal potential and jerk were independent of the applied PCN concentration in the range between 16-1,000 IU/0.5 microliter (90.5-113 s, and from 106-196 s, respectively), as well as from the injection site in the visual or motor cortex (potential: 80 vs. 69 s; jerk: 124 vs. 129 s, respectively). After epileptiform experience in the visual cortex, the latencies of the first potential and jerk were significantly (p < 0.05) increased compared to animals with an experience in the motor cortex (first potential: 100 vs. 66 s; first jerk: 159 vs. 116 s, respectively). The results show that a PCN focus in the visual cortex decreases the susceptibility of the motor cortex for the convulsant action of PCN. This means that an autoprotective mechanism is activated whose efficiency depends upon a close linkage between the visual and motor cortex.

Animals↗

Motor cortex excitability during unilateral muscle activity.

The effect of unilateral tonic muscle activity with and without co-activation of the antagonists on motor cortex excitability has been studied. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseus muscles of both hands in response to transcranial magnetic stimulation (TMS) during relax, isometric index finger abduction and antagonistic co-activation. The intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated by paired-pulse TMS with interstimulus intervals of 3 and 13 ms. The unilateral tonic activation of the right hand facilitated contralateral and ipsilateral responses (cMEP and iMEP) recorded from both hands with an exception of iMEPs recorded from the left hand. During paired-pulse TMS ICI for cMEPs was not influenced by the unilateral tonic activity in both hands, while ICF was suppressed when MEPs were recorded from the active right hand. The effect of unilateral tonic activity on iMEP in response to paired-pulse TMS was essentially different: generally, ICI was greater for iMEPs and ICF was completely abolished with an exception of iMEPs recorded from the left hand during right finger isometric abduction when a strong ICF was evident. The decreased ICF and/or increased ICI are assumed to reflect mechanisms underlying the co-activation of antagonists.

Action Potentials↗

Rapid modulation of distributed brain activity by Transcranial Magnetic Stimulation of human motor cortex.

This paper reviews the effects of single and repetitive transcranial magnetic stimuli (rTMS) delivered to one cortical area and measured across distributed brain regions using electrophysiological measures (e.g. motor thresholds, motor evoked potentials, paired-pulse stimulation), functional neuroimaging (including EEG, PET and fMRI) and behavioural measures. Discussion is restricted to changes in excitability in the primary motor cortex and behaviour during motor tasks following transcranial magnetic stimulation delivered to primary motor and premotor areas. Trains of rTMS have lasting effects on the excitability of intrinsic and corticofugal neurones, altering the responsiveness of local and remote sites. These effects lead to distributed changes in synaptic activity at rest, and during a range of motor tasks. It is possible to impair or improve performance following rTMS, but for most simple motor tasks performance is unaltered. Changes in distributed activity observed with functional imaging during motor behaviour may represent compensatory activity, enabling maintenance of performance; stimulation of additional cortical areas appears to impair performance. A detailed understanding of the distributed changes in excitability following rTMS may facilitate future attempts to modulate motor behaviour in the healthy brain and for therapeutic purposes.

Brain↗

Sequential activation of neurons in primate motor cortex during unrestrained forelimb movement.

We trained monkeys to perform an unrestrained, reaching movement of the arm. Electromyogram (EMG) recordings of forelimb muscles revealed sequential activation, proximal to distal, of muscle groups involved in the task. The delay in onset of EMG activity between proximal (shoulder and elbow) and distal (wrist and finger) muscles was approximately 60 ms. We identified the neurons in the forelimb area of the contralateral motor cortex as controlling particular joints by previously defined criteria involving responses to somatosensory stimulation and effects of intracortical microstimulation. Many cells discharged prior to the onset of EMG activity acting on the appropriate joint, whereas others began firing at a later phase of the movement. The population of all proximal cells altered discharge patterns approximately 60 ms earlier than the population of distal cells. A small percentage of cells showed an initial inhibitory change in discharge frequency, and this inhibition typically occurred prior to the excitatory changes seen in the majority of cells. The results are discussed in terms of the "nested-zone" model of the forelimb motor cortex. The data support one of the predictions of this model, namely that discharges of identified cells within the cortical zones are causally related to voluntary movement at appropriate forelimb joints.

Animals↗